How Metabolism Affects Weight Loss and Gain

This study aims to better understand why certain individuals find it difficult to lose weight while others struggle to gain weight. Investigators believe that differences in how the human body uses energy-referred to as the metabolic phenotype-may play a key role.

Two groups of participants will be compared: one group includes lean individuals who have difficulty gaining weight, and the other group consists of individuals with obesity who have difficulty losing weight. Participants will undergo a series of tests designed to measure how the human body burns calories under different conditions.

The study involves two main components:

• 24-Hour Fasting Period: Participants will abstain from eating for 24 hours to observe how the body adapts by either conserving or maintaining energy expenditure.
• Meal Test: Following the fasting period, participants will consume a specially designed, low-protein meal that simulates overeating. The investigators will measure how much additional energy is burned during digestion, a process known as diet-induced thermogenesis.

A technique called indirect calorimetry will record oxygen consumption and carbon dioxide production. These measurements help calculate resting energy expenditure (REE), which refers to the calories the body burns while at rest, and any changes that occur after fasting and eating.

The goal is to identify distinct metabolic patterns. Some individuals may have a "thrifty" metabolism that conserves energy, making weight loss more challenging, whereas others may have a "spendthrift" metabolism that expends more energy, potentially explaining difficulty in gaining weight. Understanding these differences could lead to more personalized and effective weight management strategies.

This study is conducted under strict safety and ethical standards to ensure minimal risk to participants. By examining the relationship between metabolism and weight control, the findings may pave the way for improved treatments for obesity and related weight issues.

Inclusion criteria

• Group 1 (Lean): BMI 18.5-22.0 kg/m², reporting difficulty gaining weight
• Group 2 (Obese): BMI >30 kg/m², reporting difficulty losing weight
• Healthy status as determined by medical history, physical examination, and laboratory tests
• Stable weight (less than 5% fluctuation) over the past 6 months

Exclusion criteria

• Prediabetes (HbA1c >5.6% or fasting blood glucose >100 mg/dL) or diabetes mellitus
• Conditions affecting appetite or energy expenditure (e.g., Cushing's syndrome, uncontrolled hyper-/hypothyroidism)
• Gastrointestinal disorders that impact nutrient absorption (e.g., inflammatory bowel disease, malabsorption syndromes, ulcers)
• Psychiatric conditions influencing eating behavior (e.g., active depression, anorexia nervosa, bulimia nervosa, borderline personality disorder)
• Acute, unstable cardiovascular disease requiring hospitalization within the last 6 months (e.g., stent placement)
• Cancer that required treatment in the past 5 years
• Chronic kidney disease (Stage IV or higher, per NKF criteria)
• Active infectious disease (e.g., HIV, hepatitis)
• Current nicotine use or nicotine use within the last month prior to screening
• Illicit drug use (e.g., amphetamines, cocaine, heroin, marijuana)
• Regular high-intensity physical activity (≥1 hour/day)
• Non-MRI-compatible metallic implants (e.g., artificial joints, metal plates)
• Pregnancy or breastfeeding
• Use of weight-loss medications
• Clinically significant claustrophobia
• Any other condition not mentioned above that, in the opinion of the investigator, could interfere with study participation or compromise patient safety